Infectious diseases now最新文献

Resistance of Gram-negative bacteria to the most widely used antibiotics, particularly β-lactams, is now considered as major public health problem. The main resistance mechanisms to β-lactams in Enterobacterales are the production of extended spectrum β-lactamases (ESBL) or carbapenemases, which hydrolyze virtually all β-lactams. However, a substantial proportion of carbapenem-resistant Gram-negative bacilli do not produce carbapenemase but combine overproduction of a cephalosporinase and/or ESBL with very low penem hydrolysis and reduced outer membrane permeability. The arrival of new antibacterial agents active on some of these multidrug-resistant strains, such as new β-lactam inhibitors, has marked a turning point in treatment and represents real progress. In-depth knowledge of resistance mechanisms is crucial to the choice of the most effective molecule, and their prescription requires close collaboration between microbiologists, infectious disease specialists and intensive care physicians. While these compounds are significantly more active against resistant strains than those previously available, their spectrum of activity does not cover all resistance mechanisms in Gram-negatives, nor in other bacterial species potentially involved in polymicrobial infections. The use of these new compounds does not alter antibiotic regimens in terms of duration and indication of combined antibiotic therapy, which remain very limited.

This section summarizes empirical antimicrobial treatment for the less frequent bacterial species less frequently causing infection, whether it be community-acquired or healthcare-associated. It specifies their role in different diseases and the recommended antibiotics, taking into account their natural and most common acquired resistance and the relevant pharmacokinetic-pharmacodynamic parameters. The advice of an infectious disease specialist or microbiologist is frequently needed.

Background

Experimental infection with Plasmodium falciparum results in malaria attack within a few days of exposure. However, we have regularly observed malaria attack within a short time after return, regardless of the time spent in an endemic area. We therefore aimed to assess whether the time before return and malaria attack varies according to length of stay.

Methods

We used anonymized data from the French National Reference Centre for Malaria between 2006 and 2016. We analyzed 11,823 cases aged at least 1 year and diagnosed with P. falciparum malaria 1 day to 1 year after returning to France, after a stay of 1 day to 1 year in an at-risk area.

Results

Trips had a median duration of 31 days [IQR: 19–56]. Median time between return from the endemic area and onset of malaria symptoms was 5 days [IQR: 0–10], and the median between return and malaria diagnosis was 9 days [IQR: 5–14]. Times to symptom onset or diagnosis were longer for stays of fewer than 15 days vs 15 days or more (for symptoms: 7 vs 4 days for longer stays, for diagnosis: 11 vs 9 days). For stays longer than 15 days, no variation was observed according to length of stay.

Conclusions

Aside from at-risk stays of fewer than 15 days, the time between return and malaria attack is constant and rather short, even after long stays. The 2 weeks following return should be considered as a risk period whatever the length of stay in an at-risk area.

Antibiotic-resistant tuberculosis continues to be one of the major threats to global tuberculosis control. After a hiatus of over 40 years in antituberculosis drug development, the last decade has seen a resurgence of research, yielding a number of promising compounds in the tuberculosis drug pipeline, with some that are now game changers in the treatment of MDRTB. Despite this progress, there are still obstacles restricting the use of these molecules as first-line drugs. The quick appearance of bacteria resistant to these new treatments highlights a continuing need to fuel the discovery and development of new molecules. With this in mind, alternative strategies aimed at optimizing the utilization of existing antituberculosis agents are currently under evaluation. They are focused on enhancing the efficacy of antibiotics against their bacterial targets, primarily by augmenting the quantity of antibiotic that engages with these targets. This objective can be achieved through two primary approaches: (1) Provided that toxicity concerns are not a limiting factor, increased dosing is a viable avenue, as demonstrated by rifampicin, isoniazid, and fluoroquinolones, for which escalated dosing has been effective; and (2) Employing enhancers such as drug activator boosters (ethionamide), efflux pump inhibitors, or hydrolytic enzyme inhibitors (kanamycin) can elevate the concentration of antibiotics in bacterial cells. These strategies offer the potential to mitigate antibiotic obsolescence and complement the discovery of new antibiotics.

Objectives

To evaluate the effects of the replacement of ceftriaxone by cefotaxime on the incidence of third-generation cephalosporin-resistant Enterobacterales (3GC-RE).

Patients and methods

We conducted a 24-month monocentric prospective, stepped-wedge cluster randomized controlled trial. During the control phase of the study, clinicians prescribed either ceftriaxone or cefotaxime. During the intervention phase, they systematically prescribed cefotaxime.

Results

The cefotaxime/ceftriaxone ratio was inversely correlated with the incidence of 3GC-RE. All in all, 3GC-RE incidence was 1.05 (27/25,692) acquired cases/1000 hospitalization days during the control phase and 0.54 (11/20,419) acquired cases/1000 hospitalization days during the intervention phase (incidence rate ratio [IRR] = 0.51 [0.22–1.07], p = 0.06). In multivariable analysis, intervention phase (versus control phase) (p = 0.007), cefotaxime/ceftriaxone ratio (p = 0.003) and imported 3GC-RE (p = 0.005) were associated with the incidence of acquired cases of 3GC-RE.

Conclusions

We found that replacing ceftriaxone with cefotaxime reduced the occurrence of 3GC-RE isolates. More studies are needed to confirm these results.

Introduction

In a French context of low vaccination coverage for human papillomavirus (HPV) disease, we conducted a study on pharmacy students and community pharmacists to assess their self-reported knowledge about HPV infection and vaccination and their perceptions of vaccination.

Material and methods

A prospective volunteered-based study was conducted in the French Franche-Comté region based on a questionnaire targeting pharmacy students (from the 2nd to 6th years) and community pharmacists.

Results

All in all, 220 students and 55 pharmacists completed a questionnaire. Fewer than a third knew which HPV genotypes are considered to be high-risk (p-value = 0.11) and were aware of the diversified nature of HPV-induced cancers (p-value = 0.02). Their overall level of general knowledge about vaccination was estimated to be good by 62% of students and 85% of pharmacists (p-value = 10⁻³). More than 75% of students and pharmacists considered that HPV vaccination has a positive benefit-risk balance (p-value = 0.44) but that its low coverage is due to non-confirmed adverse events that were suggested in the past (p-value = 0.60). Pharmacists had a better perception of the safety of HPV vaccination (84% versus 64%, p-value = 6·10⁻³). More than 50% of students and pharmacists agreed with mandatory HPV vaccination for girls and boys (11–14 years).

Conclusion

This study allowed us to assess the knowledge of students and community pharmacists and their more or less favorable perceptions of HPV vaccination. It helped us to suggest their needs in terms of practical training. Future changes should include pharmacists in the implementation of public health policies and to improve vaccination coverage.

Objectives

Totally implantable venous access ports (TIVAP) are devices mainly used to deliver antineoplastic chemotherapies, of which the insertion may be complicated by TIVAP-related infection (TIVAP-RI). This study aims to provide data on the risk factors for TIVAP-RI and its influence on patient prognosis.

Patients and methods

Prospective observational study including adult patients with solid tumors, in whom a TIVAP was inserted to deliver antineoplastic chemotherapy between January 2018 and October 2019. Factors associated with TIVAP-RI and one-year mortality were determined using multiple logistic regressions.

Results

More than a thousand (1014) patients were included, among whom 48 (4.7%) presented with TIVAP-RI. Gram-positive cocci and Gram-negative bacilli represented 51% and 41% of the pathogens isolated, respectively. Young age (odds ratio [OR] 0.67; 95% Confidence Interval [0.53–0.83] per 10-year increase), WHO performance status ≥ 1 (OR 3.24 [1.52–7.79]), chemotherapy administration in the month before TIVAP placement (OR 2.26 [1.17–4.26]), and radiation therapy of the homolateral chest wall (OR 3.28 [1.51–6.67]) were independently associated with TIVAP-RI occurrence. During the year following TIVAP insertion, 287 (28%) patients died. TIVAP-RI was not associated with one-year mortality (OR 1.56 [0.75–3.19]).

Conclusion

TIVAP insertion in adult patients with solid tumors is associated with a low infection rate, which did not influence one-year mortality. In addition to young age and impaired health status, TIVAP insertion in the month following initiation of the antineoplastic chemotherapy and TIVAP insertion in an irradiated area are two newly reported preventable TIVAP-RI risk factors.

Objectives

Prosthetic joint infections (PJIs) due to the Clostridium species have not been widely investigated. We aimed to characterize these uncommon infections.

Methods

We conducted a retrospective study between 2003 and 2020 in six French hospitals combined with a review of the literature.

Results

The main conclusions obtained from the 16 patients included were reinforced by the literature analysis: (i) Clostridium perfringens was the most frequently involved species, (ii) patients presented an advanced age at the time of prosthesis placement and infection, (iii) most of the infections were early- or delayed-onset, (iv) the prognosis for these PJIs remains poor, (v) when performed (n = 5), DAIR with 12-week antimicrobial therapy led to a favorable outcome in 80% of cases.

Conclusions

Given the low incidence of this infection, our work represents the largest series of clostridial PJIs reported to date and highlights some specificities of these infections. Further prospective studies are needed to confirm these results.

Introduction

We aimed to determine whether doravirine/lamivudine/tenofovir disoproxil fumarate (DOR/3TC/TDF) given 5 or 4 days a week was able to maintain viral suppression in people living with HIV (PLHIV).

Methods

In this observational, retrospective study, we included all PLHIVs who had received intermittent DOR/3TC/TDF between 10/01/2019 and 01/31/2021, in two French hospitals.

Results

Forty-three PLHIVs were included, median (IQR) age: 52 years (48–58), ART duration: 15 years (8–23), duration of virological suppression: 6 years (2–10). Median follow-up was 78 weeks (IQR 62–97). One virological failure (VF) occurred at W38 (HIV-RNA = 61 and 76 copies/mL), in a patient with no viral resistance at baseline or at time of VF, and during the study period five individuals discontinued DOR/3TC/TDF due to adverse events. There were no significant changes during follow-up in the CD4 count, CD4/CD8 ratio, body weight or residual viremia rate.

Conclusion

These findings suggest the potential for intermittent DOR/3TC/TDF to maintain virological control.